Publications by authors named "Clemens Baumbach"

9 Publications

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Residing near allergenic trees can increase risk of allergies later in life: LISA Leipzig study.

Environ Res 2020 12 24;191:110132. Epub 2020 Aug 24.

Allergens in Ecosystems, Institute of Biochemical Plant Pathology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.

Background: We investigated whether residing in places with higher greenness, more trees and more allergenic trees early in life increases the risk of allergic outcomes, and whether these associations differ depending on the concentration of air pollutants.

Methods: The analytic sample included 631 children from the German birth cohort LISA Leipzig. Asthma and allergic rhinitis, sensitization to aeroallergens and food allergens, as well as confounders, were collected prospectively up to 15 years. Greenness was assessed by Normalized Difference Vegetation Index (NDVI). A tree registry was used to derive information on trees, which were classified into allergenic and non-allergenic. Annual average concentrations of nitrogen dioxide (NO) and ozone were also used. Geographic exposures were assigned to home addresses at birth. Longitudinal associations were analysed using generalized estimating equations.

Results: Medium and high numbers (tertiles) of trees and allergenic trees in a 500 m buffer around birth addresses were associated with increased odds of allergic rhinitis up to 15 years regardless of NDVI. These exposures were also related to higher odds of sensitization to aeroallergens. Associations with asthma and sensitization to food allergens were less consistent. Effect estimates for allergic rhinitis were stronger in the high tertile of NO compared to the low tertile, while an opposite tendency was observed for ozone.

Conclusion: We observed that early life residence in places with many trees, and allergenic trees specifically, may increase the prevalence of allergic rhinitis later in life. This association and its modification by air pollution should be pursued in further studies.
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http://dx.doi.org/10.1016/j.envres.2020.110132DOI Listing
December 2020

Depression and anxiety with exposure to ozone and particulate matter: An epidemiological claims data analysis.

Int J Hyg Environ Health 2020 07 19;228:113562. Epub 2020 May 19.

Institute and Clinic for Occupational, Social and Environmental Medicine, University Hospital, Ludwig Maximilian University of Munich; Comprehensive Pneumology Center (CPC) Munich, Member DZL, German Center for Lung Research, Munich, Germany; Allergy and Lung Health Unit, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia. Electronic address:

Background: Depression and anxiety have complex etiologies and are associated with a significant burden of disease. Although air pollution has been hypothesized as a possible risk factor of these disorders, the associations are still under-investigated. We aimed to analyze associations between long-term exposure to ambient ozone and particulate matter with diameter <10 μm (PM) and diagnoses of depression and anxiety in a general population.

Methods: We utilized data from a large statutory health insurance company from Saxony, Germany. Information on outpatient clinical diagnoses of depression and anxiety was available for the years 2005-2014. We assigned ambient ozone and PM estimates to residential districts of 1.13 million individuals aged 16 and older. Depression and anxiety were defined as diagnoses counts. Associations with depression and anxiety were assessed using adjusted generalized estimating equations models.

Results: In the ten-year study period, the observed prevalences of depression and anxiety were 7.40% and 3.82%, respectively. In the two-pollutant model, 10 more days with a maximum 8-h average ozone concentration exceeding 120 μg/m³ resulted in a relative risk (RR) of 1.010 with 95% confidence interval (CI) (1.005, 1.014) for depression and an RR of 1.007 (95% CI (1.000, 1.014)) for anxiety. The effect estimates of PM for depression and anxiety were 1.180 (95% CI (1.160, 1.201)) and 1.176 (95% CI (1.148, 1.205)) per 10 μg/m³ increase in PM concentration, respectively. Age, sex, and access to healthcare of the individual were also associated with the diagnosis of the disorders. The associations were consistent across one- and two-pollutant models.

Conclusions: Our findings indicate that increased levels of ambient ozone and PM may elevate the risk of a depression or anxiety diagnosis in the general population. However, given the lack of data on individual air pollutant exposure and socioeconomic status, our results should be interpreted with caution. Further well-designed epidemiological studies should replicate our findings.
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http://dx.doi.org/10.1016/j.ijheh.2020.113562DOI Listing
July 2020

Associations of autozygosity with a broad range of human phenotypes.

Nat Commun 2019 10 31;10(1):4957. Epub 2019 Oct 31.

Department of Neurology, Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht University, Utrecht, 3584 CX, The Netherlands.

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F) for >1.4 million individuals, we show that F is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F are confirmed within full-sibling pairs, where the variation in F is independent of all environmental confounding.
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http://dx.doi.org/10.1038/s41467-019-12283-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823371PMC
October 2019

Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci.

Mol Psychiatry 2020 10 7;25(10):2392-2409. Epub 2019 Jan 7.

Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, Netherlands.

Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.
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http://dx.doi.org/10.1038/s41380-018-0313-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515840PMC
October 2020

pulver: an R package for parallel ultra-rapid p-value computation for linear regression interaction terms.

BMC Bioinformatics 2017 Sep 29;18(1):429. Epub 2017 Sep 29.

Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany.

Background: Genome-wide association studies allow us to understand the genetics of complex diseases. Human metabolism provides information about the disease-causing mechanisms, so it is usual to investigate the associations between genetic variants and metabolite levels. However, only considering genetic variants and their effects on one trait ignores the possible interplay between different "omics" layers. Existing tools only consider single-nucleotide polymorphism (SNP)-SNP interactions, and no practical tool is available for large-scale investigations of the interactions between pairs of arbitrary quantitative variables.

Results: We developed an R package called pulver to compute p-values for the interaction term in a very large number of linear regression models. Comparisons based on simulated data showed that pulver is much faster than the existing tools. This is achieved by using the correlation coefficient to test the null-hypothesis, which avoids the costly computation of inversions. Additional tricks are a rearrangement of the order, when iterating through the different "omics" layers, and implementing this algorithm in the fast programming language C++. Furthermore, we applied our algorithm to data from the German KORA study to investigate a real-world problem involving the interplay among DNA methylation, genetic variants, and metabolite levels.

Conclusions: The pulver package is a convenient and rapid tool for screening huge numbers of linear regression models for significant interaction terms in arbitrary pairs of quantitative variables. pulver is written in R and C++, and can be downloaded freely from CRAN at https://cran.r-project.org/web/packages/pulver/ .
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http://dx.doi.org/10.1186/s12859-017-1838-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622569PMC
September 2017

Genome-wide association study identifies 74 loci associated with educational attainment.

Nature 2016 05 11;533(7604):539-42. Epub 2016 May 11.

Department of Neurology, General Hospital and Medical University Graz, Graz 8036, Austria.

Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
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http://dx.doi.org/10.1038/nature17671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4883595PMC
May 2016

Directional dominance on stature and cognition in diverse human populations.

Nature 2015 Jul 1;523(7561):459-462. Epub 2015 Jul 1.

Department of Nutrition and Dietetics, Harokopio University of Athens, 70, El. Venizelou Ave, Athens, 17671, Greece.

Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
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http://dx.doi.org/10.1038/nature14618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4516141PMC
July 2015

Mitochondrial genetic variants identified to be associated with BMI in adults.

PLoS One 2014 25;9(8):e105116. Epub 2014 Aug 25.

Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität Munich, Neuherberg, Germany; Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.

It has been suggested that mitochondrial dysfunction plays a role in metabolic disorders including obesity, diabetes, and hypertension. The fact that mitochondrial defects can be accumulated over time as a normal part of aging may explain why some individuals can eat all sorts of foods and remain at normal weight while they are young. However, around the fourth decade of life there is a trend towards "middle-age spread" with weight gain and the body's decreasing ability to metabolize calories efficiently. To test the hypothesis that mitochondrial variants are associated with BMI in adults, we analyzed a total number of 984 mitochondrial single nucleotide polymorphisms (mtSNPs) in a sample of 6,528 individuals participating in the KORA studies. To assess mtSNP association while taking heteroplasmy into account we used the raw signal intensity values measured on the microarray and applied linear regression. Significant results were obtained for 2 mtSNPs located in the Cytochrome c oxidase subunit genes (MT-CO1: Padjusted = 0.0140 and MT-CO3: Padjusted = 0.0286) and 3 mtSNPs located in the NADH dehydrogenase subunit genes (MT-ND1, MT-ND2 and MT-ND4L: Padjusted = 0.0286). Polymorphisms located in the MT-CO3 and MT-ND4L genes have not been associated with BMI or related phenotypes in the past. Our results highlight the importance of the mitochondrial genome among the factors that contribute to the risk of high BMI. Focusing on mitochondrial variants may lead to further insights regarding effects of existing medications, or even to the development of innovative treatments.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0105116PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143221PMC
May 2015

Genome-wide linkage analysis of congenital heart defects using MOD score analysis identifies two novel loci.

BMC Genet 2013 May 24;14:44. Epub 2013 May 24.

Institute of Medical Informatics, Biometry, and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany.

Background: Congenital heart defects (CHD) is the most common cause of death from a congenital structure abnormality in newborns and is often associated with fetal loss. There are many types of CHD. Human genetic studies have identified genes that are responsible for the inheritance of a particular type of CHD and for some types of CHD previously thought to be sporadic. However, occasionally different members of the same family might have anatomically distinct defects - for instance, one member with atrial septal defect, one with tetralogy of Fallot, and one with ventricular septal defect. Our objective is to identify susceptibility loci for CHD in families affected by distinct defects. The occurrence of these apparently discordant clinical phenotypes within one family might hint at a genetic framework common to most types of CHD.

Results: We performed a genome-wide linkage analysis using MOD score analysis in families with diverse CHD. Significant linkage was obtained in two regions, at chromosome 15 (15q26.3, P(empirical) = 0.0004) and at chromosome 18 (18q21.2, P(empirical) = 0.0005).

Conclusions: In these two novel regions four candidate genes are located: SELS, SNRPA1, and PCSK6 on 15q26.3, and TCF4 on 18q21.2. The new loci reported here have not previously been described in connection with CHD. Although further studies in other cohorts are needed to confirm these findings, the results presented here together with recent insight into how the heart normally develops will improve the understanding of CHD.
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http://dx.doi.org/10.1186/1471-2156-14-44DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664624PMC
May 2013
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